Oxybicyclo (4.1.0.) hepta-2,4-diene-7-carboxylic esters



Patented Dec. 5, 1550 UNITED STATES 2,532,575 oFrIcE- OXYBICYCLO 1.1.0. HEPTA-2A-DIENE-7 CARBOXYLIC ESTERS No Drawing. Application November 3, 1947, Serial N0. 783,843

Claims.

This invention relates to new organic fusedring compounds. More particularly, it relates to new, fused, carbocyclic oxy-compounds and to methods for their preparation.

An object of this invention is to provide new, fused, oxy-substituted, carbocyclic compounds. A further object is to provide new, fused, oxysubstituted, carbocyclic compounds containing as an essential structural feature an oxycyclohexadiene nucleus which is part of an oxyclocloheptadiene ring. Yet a further object is to provide a method of preparation for new, fused, oXy-substituted, carbooyclic compounds of this invention. A particular object is the provision of new insecticidal materials. Other objects will appear hereinafter.

These objectsare accomplished by the produc tion of new, fused, oxy-substituted, carbocyclic compounds in which one to three oxy-substituents are directly attached through oxygen atoms to annular carbon atoms of the four-carbon conjugated diene system of a cyclohexadiene ring, the

remaining two carbon atoms of said cyclohexadiene ring, each bearing hydrogen, being common to a cyclopropane ring, the third carbon atom of the cyclopropane ring being directly attached to hydrogen and to a carboxyl group or derivatives thereof which on hydrolysis yield the carboxyl group. 7

Thus, that portion of the new compounds of the invention containing an oxycyclohexadiene ring may be represented by the structural formula wherein the oxy-substituentsare directly attached through oxygen at one to three of the positions designated as 2,3, 4 and 5, and A is carlooxyl and its derivatives which form carboxyl when subjected to hydrolyzing conditions. The oxy-substituents, OR, attached to the above cyclohexadiene ring consist of the hydroxyl group and alkoxy groups obtainable therefrom, R representing hydrogen and alkyl groups, preferably of from one to six carbon atoms. A is carboxyl and its derivatives which form carboxyl when subjected to hydrolyzing conditions.

bonded to hydrogen, halogen and monovalent.

hydrocarbon radicals, preferably alkyl of from .one to six carbon atoms, and divalent hydrocarbon radicals whereinthe two valenoes, preferably 2. of a four-carbon conjugated diene radical, are joined to adjacent annular carbon atoms in positions 2, 3 or 4, 5 of said cyclohexadiene ring. The new compounds of the invention are obtained by reacting a phenolic-0x3 compound with a diazoacetic ester at a temperature between the range of 80 and 180 C., said phenolic-oxy compound consisting of benzenoid compounds containing 1 to 3 ring-attached hydroxyl groups and their alkyl ethers, and having, in such oxy-substituted aryl ring, at least tWo nuclear vicinal carbon atoms bearing hydrogen.

In a specific embodiment of the invention, 2 to 6 moles of an alkyl phenyl ether having at least two nuclear vicinal carbon atoms bearing hydro:

. gen are reacted at a temperature between the range of and 180 C. With a molal amount of an alkyl diazoacetic ester and the oxybicyclo- (4.1.0)hepta-2,4 diene 7 carboxylic ester so formed is isolated by distillation.

The reaction is specifically illustrated with pchloroanisole and ethyl diazoacetate:

OCH;

i no on 5 II +mcn-c0oonn n on oH-oooonn N, H

o H h The following examples in which parts are by Weight unless otherwise indicated illustrate the practice of the invention.

Emample I an equal volume of methylene chloride and, after filtering off the copper bronze, was distilled through a short open column. Upon redistillae tion and fractionation from an 18" saddle-packed column, 20.6' parts (29% of the theoretical amount) 'of slightly yellow, fragrant, oily ethyl 3 1.5019. This compound can be represented by the.

following formula:

CHC O 02115 AnaZ.Calcd. for Ciel-113032 C, 66.70; H, 6.72. Found: C, 66.40; H, 6.70..

Example II A mixture of 40 parts (0.85 mole) of ethyl diazoacetate and an equimolar amount of anisole Was added dropwise to 151.5 parts (1.40 moles) of anisole previously heated to 154-5 C. Nitrogen was evolved almost immediately. After all of the esterhad been added (about 1.25 hrs.) the reflux temperature was maintained for an additional hour until the evolution of nitrogen had ceased. The product was first distilled through an empty column and then redistilled through a column packed with Fenske rings The redistilled product consisted of 18.8 parts (27.6% of the theoretical amount) of yellow, oily ethyl 3-methoxybicyclo (4.1.0)hept'a-2,4-diene-7-carboxylate boiling between 95-1'05 C./1.15-1.20 mm, with a refractive index of 11 1.5185. This compound can be represented by the following formula:

OCH;

AnaZ.-Calcd. for CiiH14O3: c, 68.0%; H, 7.27%. Found: 0, 67.72%, 67.62%; H, 7.49%, 7.25%.

Example III A solution of 28.5 parts (0.25 mole) of ethyl diazoacetate in 35.6 parts (0.2.5 mole) of p-chloroanisole was added with stirring to 35.6 parts (0.25 mole) of p-chloroanisole heated at 140 C. At this temperature the reaction became exothermic with the evolution of nitrogen and at about 156 C. the evolution of heat was sufficient to make the reaction self-propagating. The total reaction time was 1.5 hours, after which the evolution of nitrogen had ceased. There was thus obtained by this procedure 6.35 parts (11.1% of the theoretical amount) of ethyl 5-chloro-2methoxybicyclo (4.1.0) hepta-2,4-diene-7-carboxylate. This product distilled between 108 C./0.55 mm. and 117 C./0.70 mm. This compound can be represented by the following formula:

OCHa

CH0 0 O CzHu AnaZ.-Calcd. for C11Hl3c103I Found: Cl, 13.73%.

Emample IV ethyl othermic to maintain the above temperature which was held between 140 and 146 C. by external heating during 37 minutes of addition time and for a subsequent period of minutes, at the end of which time the nitrogen evolution had ceased. Following a distillation through a 6 open column, the product was redistilled through a 6" column packed with Fenske rings. A yield of' 8.6 parts (15.4% of the theoretical amount) of 2,4-dimethoxybicyclo (4.1.0) hepta-ZKl-di" ene-7-carboxylate, a fragrant yellow oil boiling between 114.5 C./0.15 mm. and l22.5 C./1.2-5 mm. was obtained The refractive index of this product, was n 1.5152. This compound can be represented by the following formula:

Anal-Calcd. for C12H1604I C, 64.25%; 7.17%. Found: C, 63.44%;11, 7.28%.

Example V To 73.5 parts (0.5 mole) of alpha-methoxynaphthalene containing approximately 50 mg. of hydroquinone, there was added at room temperature 28.5 parts (0.25 mole) of ethyl diazoacetate. Very little nitrogen was evolved until the temperature had been raised to 145 C., at which point the reaction became moderately exothermic. During the time of addition (48 minutes) and for 25 minutes following, the temperature was maintained between and C. Heating was continued at -165 C. for 25 additional minutes until the evolution of the nitrogen had ceased. After purification of the product by distillation as described in Example IV, 11 parts (18.1% of the theoretical amount) of ethyl 3-methoxy-1a,7b-dihydro-l-cyclopropa- [a]-naphthalene-l-carboxylate, a yellowish oil boiling between 135 and 144 C./0.07 mm. was obtained. This compound is a derivative of the generic bicyclo structure given on page 2 and may also be named ethyl 4-methoxybenzo(b)- bicyclo (4.1.0) hepta-2,4-diene-7-carboxylate. De-

ermination of refractive index on this product gave a value of 11 1.5641. This compound can be represented by the following formula:

OCHz H H CHCOOCzHs AnaZ.Ca1cd. for C15H16O32 C, 73.70%; H, 6.59%. Found: C, 71.92%, 71.56%; H, 7.08%, 6.78%.

Example VI (A) The procedure of Example II was repeated essentially as described, using 91.5 parts (0.75 mole) of phenetole in place of anisole with 28.5 parts (0.25 mole) of ethyl diazoacetate. The reaction temperature was allowed to rise as high as C. and, as the reaction proceeded, nitrogen was evolved vigorously. The ethyl 3-ethoxybicyclo- (4.1.0) hepta-2,4-diene-7-carboxylate was obtained in 17.2% yields as a yellow oil boiling at 91-995 C./0.3-1.38 mm. and having a refractive index of 11. 1.5068. This compound can b lepr ficrlted by the following formula:

OCzHs H CHCO O C2115 (B) Higher alkyl esters can also be prepared by the general procedures described above. For example, Z-ethylhexyl 3-methoxybicyclo(4.1.0)- hepta-2,4-diene-7 carboxylate was obtained by the procedure described under Example II through replacement of the ethyl diazoacetate with 2-ethylhexyl diazoacetate. This ester, obtained in 17.4% yield as a yellow oil distilled at 146-156 C./0.75 mm.and possessed a refractive index of 11. 1.4871. This compound can be represented by the following formula:

OCH; H

/OEOOOCH2 |JHO4H0 AnaZ.-Calcd. for 0171-12603: C, 73.25%? H,

'A'naZr-Calcd. for C13H1a032 C, 70.3%; H, 8.1%. Found: C, 68.79%, 68.98%; H, 8.14%, 8.21%.

It is to be understood that both the 2- and 3-oxy-substituted bicyclo(4.1.0) hexa 2,4 diene carboxylic esters, as well as mixtures of the two position isomers which are possible, are meant to be included within the scope of this invention.

The phenolic-oxy compounds used to prepare the new compounds of this invention can be represented by the general formula AI(O-R)n, wherein n is one to three, but preferably one to two, R is hydrogen and alkyl groups, preferably of up to 6 carbon atoms, e. g., methyl, ethyl, propyl, isopropyl, but l, isobutvl, tertiary-butyl, n-amyl, isoamyl, n-hexyl, etc., and Ar is an aryl group in which such oxy-substituted aryl ring also contains at least two nuclear vicinal carbon atoms bearing hydrogen. Although the aryl group can be of one or more carbocyclic rings, it is preferred to use those of the benzene,'nanhthalene, phenanthrene, and anthracene class and, still more preferably, those of the benzene and naphthalene class, since thephenolic-oxy compounds of this type give the most useful fused, oXy-substituted, carbooyclic compounds. The aryl groups can a so contain other substituents, preferably neutral substituents, e. g., hydrocarbon radicals, preferably alkyl radicals of 1 to 6 carbon atoms, such as methyl, ethyl, tertiary-butyl, amyl, hexy l, etc.; halogen such as fluorine, chlorine, and bromine. Examples of these aryl groups include phenyl, tolyl, xylyl, chlorophenyl, bromophenyl, fiuorophenyl, naphthyl, chloronaphthyl, alpha-methylnaphthyl,

beta-methylnaphthyl, henanthryl, anthracyl, and the like.

By suitably reacting, in accordance with the general procedures of the illustrative examples, a diazoacetic ester, e. g., ethyl diazoacetate, with such phenolic-oxy compounds as 1-hydroxy-4- chlorobenzene, 1-hydroxy-4-bromobenzene, 1- hydroxy-Z-methylbenzene, l-hydroxy-S-methylbenzene, l hydroxy 4 methylbenzene, 1-hydroxy-4-tertiary-butylbenzene, 1,2 dihydroxybenzene, 1,3-dihydroxybenzene, 1,4-dihydroxybenzene, 1,3-dihydroxy-4-methylbenzene, 1,2,3- trihydroxybenzene, 2-hydroxy-1-chloronaphtha lene, 2,6 dihydroxynaphthalene, 1 hydroxyphenanthrene, l-hydroxyanthracene, n-propoxybenzene, n-butoxy-benzene, 1-methoxy-4-bromobenzene, l-methoxy-4-fluorobenzene, l-ethoxy-2- bromobenzene, 1-methoxy-4-methylbenzene, 1- methoXy-Z,4-dimethylbenzene, l-methoxy 2,5- dimethylbenzene, I1,2,3-trimethoxybenzene, 2- methoxy-l-chlorqnaphthalene, 2,5-dimethoxynaphthalene, z-methoxyphenanthrene, 4-methoxy-phenanthrene, 2-methoxyanthracene, other new fused, oxy-substituted, carbocyclic compounds of the invention aside from those already recited can be obtained. For example, from ethyl diazoacetate and 1methoxy-4-methylbenzene, ethyl .5-methyl-Z-methoxy-bicyclo (4.1.0) hepta- 2,4-diene-7-carboxylate is obtained. Others which can be obtained include ethyl 5amy1-2 methoxy bicyclo(4.1.0)hepta 2,4 diene '7- carboxylate, ethyl 3-n-hexoxy-bicyclo(4.1.0)- hepta-2,4-diene-7-carb0xylate, and the like.

The cyclopropane substituents, i. e., those attached directly through carbon at the 7-position Of the cyclo hepta-2,4-diene ring as designated herein, which fall within the scope of the invention, are hydrolyzable to the carboxyl group and include carboxylic esters, amides, halides,

anhydrides, salts, and the nitrile, aside from carboxyl. The alkyl carboxylic esters of up to 12 carbon atoms are preferred since they are the most readily accessible.

New fused, oxy-substituted, carbocyclic compounds containing these cyclopropane substituents at the above designated position can be obtained in accordance with the following scheme of well-known reactions:

Cycolopropane-linkcd ester (0 O 0 R) Hydrolysis with Hydrolysis with bromide (C0 C1, or -O OBr) 7 Acid anhydride (-0 O O O C-) Ester, acid, acid chloride or bromide, or acid anhydride Secondary amine (RzNH) tertiary acyl amine (-C ONRQ) secondary acyl amine (-C ONH R) Primary amine (RNH?) M primary acyl amine (-CONHz) dehydrating 1 agent, e.g. P20

nitrile (-CN) R is a monovalent saturated hydrocarbon radical; M is an alkali metal.

The diezp ce s ester su abl cmslp l the. processbf this invention havethe'ge r'a ly mulaNz ciieg gon, wherein R, is afr'nonovalent saturate hydrocarbon radical of the. acyclic. and, alicyclic series, preferabl alkyl of up. to 12 carhon'atoms. Examples of such radicals include methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl. amyljhex yl, cyclohexyl, octyl, dodecyl, etc.

In the process of. this'invention the molal ratio of phenolie-oxy compound to diazoacetic ester may vary. from 1:1" to. 20.11. Preferably, there should be a molal excess of the phenolic-oxy compound. The nol al ratio most preferred is that within the range of 2:1 to 6:1 since, in general, with h se. mps of phenol c- X31 ompound to. diagioacetic ester, the reaction proceeds with less, side. reaction, by products.

The, reaction is usually carried out at a tem perature where nitrogen is evolved freely and can from 29 to 39 C. below the" decomposiien. poin e the ea an o ea v pr d c n ra t e; a t m e a ure of i a-1 is preferred. The time of reaction depends upon the temperature and may vary from 1 to as much as 2 4 hours depending, to a large extent, on the completion of nitrogen evolution. Ordinarily, at the preferred temperature range, 3 to 5 hours reaction time issuihcient for optimum results.

The new, fused, orgy-substituted, carbocyclic compounds of the invention which, in general, are viscous, oily, light-colored liquids of pleasant odors, include mixtures of cis-trans isomers and alsopesition isomers, i. e., mixtures of position isomers wherein the two common annular carbon, a ms 9 he, c lp r ane n an the ycyciohexadiene ring are either in an ortho-meta, or metaepara position relative to an oxy-subale as her in d fined The new compounds of this invention are usell f r va i us mcie p r e They may be used as plasticize s, as intermediates for pharmaceuticals; and in perfume, bactericidal and insecticidal compositions. The products of am l s I and I whe ray d as acetone solutions effected 109 and 92% kill, respectively, against red spiders. Some. of these products are also useful as insect paralyzants, especially toward housefiies and mosquitoes. For example, the product of Example IL, when sprayed in 1% concentration in an acetone-kerosene (Deobase) solution (9 parts-1 part, by volume) against housefiies, paralyzes 83% of the flies in 10 min utes. A similar test against cockroaches paralyzes 55% in the same time.'

As many apparently widely different embodiments of this invention may be made without departing from the spirit and scope thereof, it is to be understood that this invention is not limited to the specific embodiments thereof except as defined in the appended claims.

I claim:

1. An ester of a fused ring carbocyclic compound consisting of a cyclopropane ring fused with an airy-substituted cyclohexadiene ring having a four-carbon atom conjugated diene system, said ester having the following structural formula wherein GR is selected from the, class consisting of the hydroxyl group and alko g'y. groups of from 1 to 6 carbon atoms, as is an integer from 1 to 2 inclusive, each OR group is directly attached through the oxygen thereof to an annular carbon atom of the four-carbon atorn conjugated diene system of said cycloheiiadiene ring, R is 'a'saturated monovalent hydrocarbon radicalof from 1 to 12 carbon atoms, at least one of the annular carbon atoms of the fourfcarbon atom conjugated diene system of said cyclohexadiene ring is directly attached ta a hydrogen atom and any remaining annular. carben atoms of the four a o t m on uga ene s t m 'oi'sa cyclohexadiene ring are each directly attached to a er elect dfr m t e Class ns stin of hydrogen, halogen, alkyl radicals of from 1 to 6 carbon atoms and a divalent four-carbon atom conjugated diene radical having terminal valences which are directly attached to adjacent doubly-bonded annular carbon atoms of said cyclohexadiene ring.

2. An ester of a fused ring carbocyclic compound. consisting of a cyelopropane ring with an oxy-substituted cyclohexadiene ringhavs a four-car on o c n u ate dien SY tem, said ester having the following structural formula wherein n is an integer from 1 to 2 inclusive, each OH group is directly attached through the oxygen thereof to an annular carbon atom of the fourcarbon atom conjugated diene system of said cyclohexadiene ring, R. is a saturated mcnovalent hydrocarbon radical of from 1 to 12 carbon atoms, and the remaining annular carbon atoms of the four-carbon atom conjugated diene system of said cyclohexadiene ring are each'directly attached toa hydrogen atom.

' 3. An ester' of 'a fused ring carbocyclic compound consisting of a cycloprop'ane ring fused with an oxysubstituted cyclohezgadiene ring having 'a four-carbon atom conjugated diene system, said 'st'er having the' following structural formula 4 wherein OR, is an alkoxy radical of from 1 to 6 carbon atoms, 72 is an integer from 1 to 2 inclusive, each OR group is directly attached through the oxygen thereof to an annular carbon atom of the four-carbon atom conjugated diene system of said cyclohexadiene ring, R is a saturated monovalent hydrocarbon radical of from 1 to 12 carbon atoms and the remaining annular qn om o the pun ar n atom r gated diene system of said cyclohe zadiene ring are each directly attached to a hydrogen atom.

4. An ester of a fused ring carbocycl'ic comwnd sensin O 5% g s lg r a e in ith sns'e s ltsd oh 'a 'er s "ring av ng f rr a bon pa aunt d ene system, said ester having the following structural formula i i on-ooon' wherein n is an integer from 1 to 2 inclusive, each OCI-Is group is directly attached through the oxygen thereof to an annular carbon atom of the four-carbon atom conjugated diene system of said cyclohexadiene ring, R. is a saturated monovalent hydrocarbon radical of from 1 to 12 carbon atoms and the remaining annular carbon atoms of the four-carbon atom conjugated diene system of said cyclohexadiene ring are each directly attached to a hydrogen atom.

5. An ester of a fused ring carbocyclic compound consisting of a cyclopropane ring fused with an oxy-substituted cyclohexadiene ring having a four-carbon atom conjugated diene system, said ester having the following structural formula carbon atoms, the OR group is directly attached through the oxygen thereof to an annular carbon atom of the four-carbon atom conjugated diene system of said cyclohexadiene ring, R is a saturated monovalent hydrocarbon radical of from 1 to 12 carbon atoms, one of the annular carbon atoms of the four-carbon atom conjugated diene system of said cyclohexadiene ring is directly attached to a hydrogen atom and the remaining annular carbon atoms of the fourcarbon atom conjugated diene system of said cyclohexadiene ring are directly attached to a divalent four-carbon atom conjugated diene radical having terminal valences which are directly attached to adjacent doubly-bonded annular carbon atoms of said cyclohexadiene ring.

6. An ester of a fused ring carbocyclic compound consisting of a cyclopropane ring fused with an oxy-substituted cyclohexadiene ring having a four-carbon atom conjugated diene system, said ester having the following structural formula I wherein OR is an alkoxy radical of from 1 to 6 carbon atoms, 12 is an integer from 1 to 2 inclusive, each OR group is directly attached through the oxygen thereof to an annular carbon atom of the four-carbon atom conjugated diene system of said cyclohexadine ring, R is a saturated monovalent hydrocarbon radical of from 1 to 12 carbon atoms, at least one of the annular carbon atoms of the four-carbon atom conjugated diene system of said cyclohexadiene ring is directly attached to a hydrogen atom and any remaining annular carbon atoms of the fourcarbon atom conjugated diene system of said cyclohexadiene ring are each directly attached to an alkyl radical of from 1 to 6 carbon atoms.

7. An ester of a fused ring carbocyclic compound consisting of a cyclopropane ring fused with an oxy-substituted cyclohexadiene ring having a four-carbon atom conjugated diene system, said ester having the following structural formula wherein OR is an alkoxy radical of from 1 to 6 carbon atoms, 11. is an integer from 1 to 2 inclusive, each OR group is directly attached through the oxygen thereof to an annular carbon atom of the four-carbon atom conjugated diene system of said cyclohexadiene ring, R is a saturated monovalent hydrocarbon radical of from 1 to 12 carbon atoms, at least one of the annular carbon atoms of the four-carbon atom conjugated diene system of said cyclohexadiene ring is directly attached to a hydrogen atom and. any remaining annular carbon atoms of the fourcarbon atom conjugated diene system of said cyclohexadiene ring are each directly attached to chlorine. V

8. The chemical compound, ethyl 3-hydroxybioyclo- (4.1.0) hepta-2,4-diene-7 -carboxylate.

9. The chemical compound, ethyl 3-methoxybicyclo- (4.1.0) hepta2,4-diene-7-carboxylate.

10. The chemical compound, ethyl 4-methoxybenzo(b) bicyclo(4.1.0)hepta-2,4-diene-7-carboxylate.

NORMAN E. SEARLE.

REFERENCES CITED The following references are of record in the file of this patent:

vol. 4411, pp. 

1. AN ESTER OF A FUSED RING CARBOCYLIC COMPOUND CONSISTING OF A CYCLOPROPANE RING FUSEED WITH AN OXY-SUBSTITUTED CYCLOHEXADIENE RING HAVING A FOUR-CARBON ATOM CONJUGATED DIENE SYSTEM, SAID ESTER HAVING THE FOLLOWING STRUCTURAL FORMULA 